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Hepatic transcriptome profiling reveals early signatures associated with disease transition from non-alcoholic steatosis to steatohepatitis 肝脏转录组分析揭示了疾病从非酒精性脂肪变性向脂肪性肝炎转变的早期特征
Liver Research Pub Date : 2022-12-01 DOI: 10.1016/j.livres.2022.11.001
Nancy Magee , Forkan Ahamed , Natalie Eppler , Elizabeth Jones , Priyanka Ghosh , Lily He , Yuxia Zhang
{"title":"Hepatic transcriptome profiling reveals early signatures associated with disease transition from non-alcoholic steatosis to steatohepatitis","authors":"Nancy Magee ,&nbsp;Forkan Ahamed ,&nbsp;Natalie Eppler ,&nbsp;Elizabeth Jones ,&nbsp;Priyanka Ghosh ,&nbsp;Lily He ,&nbsp;Yuxia Zhang","doi":"10.1016/j.livres.2022.11.001","DOIUrl":"10.1016/j.livres.2022.11.001","url":null,"abstract":"<div><h3>Background and aim</h3><p>Non-alcoholic fatty liver disease (NAFLD) is becoming a leading cause of chronic liver disease worldwide. The molecular events that influence disease progression from non-alcoholic fatty liver (NAFL) to aggressive non-alcoholic steatohepatitis (NASH) remain incompletely understood, leading to lack of mechanism-based targeted treatment options for NASH. This study aims to identify early signatures associated with disease progression from NAFL to NASH in mice and humans.</p></div><div><h3>Materials and methods</h3><p>Male C57BL/6J mice were fed a high-fat, -cholesterol, and -fructose (HFCF) diet for up to 9 months. The extent of steatosis, inflammation, and fibrosis was evaluated in liver tissues. Total RNA sequencing (RNA-seq) was conducted to determine liver transcriptomic changes.</p></div><div><h3>Results</h3><p>After being fed the HFCF diet, mice sequentially developed steatosis, early steatohepatitis, steatohepatitis with fibrosis, and eventually spontaneous liver tumor. Hepatic RNA-seq revealed that the key signatures during steatosis progression to early steatohepatitis were pathways related to extracellular matrix organization and immune responses such as T cell migration, arginine biosynthesis, C-type lectin receptor signaling, and cytokine-cytokine receptor interaction. Genes regulated by transcription factors forkhead box M1 (FOXM1) and negative elongation factor complex member E (NELFE) were significantly altered during disease progression. This phenomenon was also observed in patients with NASH.</p></div><div><h3>Conclusions</h3><p>In summary, we identified early signatures associated with disease progression from NAFL to early NASH in a mouse model that recapitulated key metabolic, histologic, and transcriptomic changes seen in humans. The findings from our study may shed light on the development of novel preventative, diagnostic, and therapeutic strategies for NASH.</p></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"6 4","pages":"Pages 238-250"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9977163/pdf/nihms-1856467.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9372128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 4
Iron metabolism in non-alcoholic fatty liver disease: A promising therapeutic target 铁代谢在非酒精性脂肪肝中的作用:一个有前景的治疗靶点
Liver Research Pub Date : 2022-12-01 DOI: 10.1016/j.livres.2022.09.003
Hanqing Chen
{"title":"Iron metabolism in non-alcoholic fatty liver disease: A promising therapeutic target","authors":"Hanqing Chen","doi":"10.1016/j.livres.2022.09.003","DOIUrl":"10.1016/j.livres.2022.09.003","url":null,"abstract":"<div><p>Non-alcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease worldwide, and is closely associated with the increased risk of the prevalence of obesity and diabetes. NAFLD begins with the presence of &gt;5% excessive lipid accumulation in the liver, and potentially develops into non-alcoholic steatohepatitis, fibrosis, cirrhosis and hepatocellular carcinoma. Therefore, insight into the pathogenesis of NAFLD is of key importance to its effective treatment. Iron is an essential element in the life of all mammalian organisms. However, the free iron deposition is positively associated with histological severity in NAFLD patients due to the production of reactive oxygen species via the Fenton reaction. Recently, several iron metabolism-targeted therapies, such as phlebotomy, iron chelators, nanotherapeutics. and ferroptosis, have shown their potential as a therapeutic option in the treatment of NAFLD and as a clinical strategy to intervene in the progression of NAFLD. Herein, we review the recent overall evidence on iron metabolism and provide the mechanism of hepatic iron overload-induced liver pathologies and the recent advances in iron metabolism-targeted therapeutics in the treatment of NAFLD.</p></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"6 4","pages":"Pages 203-213"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2542568422000459/pdfft?md5=f2e918de620676f2d2273542e7b15c28&pid=1-s2.0-S2542568422000459-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43790882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 4
Corrigendum to <’Deficiency of pyruvate dehydrogenase kinase 4 sensitizes mouse liver to diethylnitrosamine and arsenic toxicity through inducing apoptosis’>Liver Research volume 2 (2018) 100–107 更正肝脏研究卷2 (2018)100-107
Liver Research Pub Date : 2022-11-01 DOI: 10.1016/j.livres.2022.11.004
Jonathan Choiniere, Matthew Junda Lin, Li Wang, Jianguo Wu
{"title":"Corrigendum to <’Deficiency of pyruvate dehydrogenase kinase 4 sensitizes mouse liver to diethylnitrosamine and arsenic toxicity through inducing apoptosis’>Liver Research volume 2 (2018) 100–107","authors":"Jonathan Choiniere, Matthew Junda Lin, Li Wang, Jianguo Wu","doi":"10.1016/j.livres.2022.11.004","DOIUrl":"https://doi.org/10.1016/j.livres.2022.11.004","url":null,"abstract":"","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48282966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Impact of antibiotics on the efficacy of immune checkpoint inhibitors in the treatment of primary liver cancer 抗生素对免疫检查点抑制剂治疗原发性癌症疗效的影响☆
Liver Research Pub Date : 2022-09-01 DOI: 10.1016/j.livres.2022.05.004
Jia-Ren Wang , Rui-Ning Li , Chao-Yi Huang , Chang Hong , Qi-Mei Li , Lin Zeng , Jing-Zhe He , Cheng-Yi Hu , Hao Cui , Li Liu , Lu-Shan Xiao
{"title":"Impact of antibiotics on the efficacy of immune checkpoint inhibitors in the treatment of primary liver cancer","authors":"Jia-Ren Wang ,&nbsp;Rui-Ning Li ,&nbsp;Chao-Yi Huang ,&nbsp;Chang Hong ,&nbsp;Qi-Mei Li ,&nbsp;Lin Zeng ,&nbsp;Jing-Zhe He ,&nbsp;Cheng-Yi Hu ,&nbsp;Hao Cui ,&nbsp;Li Liu ,&nbsp;Lu-Shan Xiao","doi":"10.1016/j.livres.2022.05.004","DOIUrl":"10.1016/j.livres.2022.05.004","url":null,"abstract":"<div><h3>Background and aim</h3><p>Immune checkpoint inhibitors (ICIs) are widely used in the treatment of liver cancer. However, the interaction with other drugs may change the efficacy of ICIs. Few studies investigated the effects of antibiotics (ATBs) on the efficacy of immunotherapy and the survival of patients with primary liver cancer receiving immunotherapy. This study aimed to explore the impact of ATBs on the efficacy of immunotherapy in patients with primary liver cancer.</p></div><div><h3>Methods</h3><p>In total, 215 patients with primary liver cancer who received ICIs from June 2018 to October 2020 were included for retrospective analysis. The progression-free survival (PFS), disease control rate (DCR), and overall survival (OS) were compared between patients treated with and without ATBs within 30 days before and after immunotherapy.</p></div><div><h3>Results</h3><p>No significant differences in PFS (<em>P</em> = 0.376) and OS (<em>P</em> = 0.121) were found between patients treated with and without ATBs. Univariate and multivariate analyses showed that using ATBs was not associated with PFS, DCR, and OS.</p></div><div><h3>Conclusion</h3><p>The use of ATBs within 30 days before and after immunotherapy in patients with primary liver cancer had no adverse effects on PFS, DCR, and OS.</p></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"6 3","pages":"Pages 175-180"},"PeriodicalIF":0.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2542568422000228/pdfft?md5=d885f83d21f0312736ae12d0b3bf3841&pid=1-s2.0-S2542568422000228-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45562982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
Efficacy and safety of low-dose rifampicin in patients with benign intrahepatic cholestasis 低剂量利福平治疗良性肝内胆汁淤积症的疗效和安全性
Liver Research Pub Date : 2022-09-01 DOI: 10.1016/j.livres.2022.08.006
Xiaoyan Guo, Xinhua Li, Ying Yan, Huijuan Cao, Yufeng Zhang, Jing Lai
{"title":"Efficacy and safety of low-dose rifampicin in patients with benign intrahepatic cholestasis","authors":"Xiaoyan Guo,&nbsp;Xinhua Li,&nbsp;Ying Yan,&nbsp;Huijuan Cao,&nbsp;Yufeng Zhang,&nbsp;Jing Lai","doi":"10.1016/j.livres.2022.08.006","DOIUrl":"10.1016/j.livres.2022.08.006","url":null,"abstract":"<div><h3>Background and aim</h3><p>Some previous studies supported that rifampicin was an effective treatment for benign intrahepatic cholestasis. However, the efficacy and safety of rifampicin remain unclear. Therefore, this study aimed to evaluate its efficacy and safety on benign intrahepatic cholestasis.</p></div><div><h3>Methods</h3><p>A retrospective, single-center, observational study was conducted on patients diagnosed with benign intrahepatic cholestasis between 2019 and 2021, who were administered 150 mg of rifampicin orally once a day. We collected and analyzed the data at baseline and post-treatment, including total bilirubin (TBIL), direct bilirubin (DBIL), total bile acid (TBA), gamma-glutamyl transferase (GGT), alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase levels. Statistical analysis was performed using appropriate tests.</p></div><div><h3>Results</h3><p>A total of 17 rifampicin-treated patients were enrolled in the study from January 2019 to January 2021. Among them, 14 patients (82%) improved, with significantly decreased TBIL, DBIL, and TBA levels after 3 weeks of treatment (all <em>P</em> &lt; 0.05), whereas the remaining 3 had no improvement. Moreover, GGT levels of the former were significantly lower than those of the latter (34 (12–227) U/L <em>vs</em>. 244 (76–293) U/L, <em>P</em> = 0.023) at baseline. No severe adverse effect was observed during treatment.</p></div><div><h3>Conclusions</h3><p>Low-dose rifampicin (150 mg per day) was an effective and safe treatment for benign intrahepatic cholestasis. Low GGT level at baseline and a significant decrease of TBIL, DBIL, and TBA levels within the first 3 weeks of treatment may lead to the good curative effect.</p></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"6 3","pages":"Pages 181-185"},"PeriodicalIF":0.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2542568422000423/pdfft?md5=f03f83d7ab84e7b61cd7ef305c3d4f49&pid=1-s2.0-S2542568422000423-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46411178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Berberine enhances the anti-hepatocellular carcinoma effect of NK92-MI cells through inhibiting IFN-gamma-mediated PD-L1 expression 小檗碱通过抑制ifn - γ介导的PD-L1表达增强NK92-MI细胞的抗肝癌作用
Liver Research Pub Date : 2022-09-01 DOI: 10.1016/j.livres.2022.08.003
Kunyuan Wang , Chengxin Gu , Ganxiang Yu , Jiaen Lin , Zhilei Wang , Qianting Lu , Yangzhi Xu , Dan Zhao , Xiaofeng Jiang , Weijian Mai , Shiming Liu , Hui Yang
{"title":"Berberine enhances the anti-hepatocellular carcinoma effect of NK92-MI cells through inhibiting IFN-gamma-mediated PD-L1 expression","authors":"Kunyuan Wang ,&nbsp;Chengxin Gu ,&nbsp;Ganxiang Yu ,&nbsp;Jiaen Lin ,&nbsp;Zhilei Wang ,&nbsp;Qianting Lu ,&nbsp;Yangzhi Xu ,&nbsp;Dan Zhao ,&nbsp;Xiaofeng Jiang ,&nbsp;Weijian Mai ,&nbsp;Shiming Liu ,&nbsp;Hui Yang","doi":"10.1016/j.livres.2022.08.003","DOIUrl":"10.1016/j.livres.2022.08.003","url":null,"abstract":"<div><h3>Background and aims</h3><p>Berberine is one of the most promising clinically tested natural alkaloids, and immunotherapy using natural killer (NK) cells is a potentially effective treatment for hepatocellular carcinoma (HCC). This study aims to elucidate the effect of berberine on the anti-HCC effect of NK92-MI cells.</p></div><div><h3>Materials and methods</h3><p>Human HCC SMMC-7721 and Hep3B cells were co-incubated with NK92-MI cells, berberine (60 or 80 μmol/L), or their combination for 36 h. To evaluate the killing effect of NK92-MI cells on HCC cells, the release of lactate dehydrogenase (LDH) in HCC cells was measured. The anti-tumor effects of berberine, NK92-MI cells, and their combinations were evaluated by MTS, EdU, Tunel, and Western blot assays. A male BALB/c nude mouse subcutaneous tumor model was used to investigate the anti-HCC effect of berberine and NK92-MI cells <em>in vivo</em>.</p></div><div><h3>Results</h3><p>The LDH assay showed that berberine enhanced the cytotoxicity of NK92-MI cells on HCC cells. The combination of berberine and NK92-MI cells demonstrated more obvious anti-HCC effect than did the berberine or NK92-MI single treatment in inhibiting cell proliferation and inducing apoptosis both <em>in vitro</em> and <em>in vivo</em>. Mechanistically, the expression of programmed cell death-ligand 1 (PD-L1) in HCC cells was upregulated after co-culture with NK-92MI cells. PD-L1 expression was knocked down, thereby inhibiting the proliferation and promoting apoptosis of HCC cells, and inhibited by berberine that blocked the secretion of interferon gamma (IFN-γ), thereby enhancing the anti-tumor effect of NK92-MI cells.</p></div><div><h3>Conclusions</h3><p>Current data show that the immunomodulatory role of berberine is to enhance the cytotoxic effect of NK92-MI cells and inhibit tumor immune escape by reducing the expression of PD-L1. Our study provides a rationale for the clinical application of berberine in combination with NK cells for the treatment of HCC.</p></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"6 3","pages":"Pages 167-174"},"PeriodicalIF":0.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2542568422000393/pdfft?md5=9a6fe0da7ef4d2aef15efde414e3c243&pid=1-s2.0-S2542568422000393-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"55273550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Wu Mengchao: A blade warrior against liver cancer 吴孟超:对抗肝癌的刀锋战士
Liver Research Pub Date : 2022-09-01 DOI: 10.1016/j.livres.2021.11.002
Tian Yang, Qi Zhang, Ming-Da Wang, Feng Shen
{"title":"Wu Mengchao: A blade warrior against liver cancer","authors":"Tian Yang,&nbsp;Qi Zhang,&nbsp;Ming-Da Wang,&nbsp;Feng Shen","doi":"10.1016/j.livres.2021.11.002","DOIUrl":"10.1016/j.livres.2021.11.002","url":null,"abstract":"","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"6 3","pages":"Pages 130-131"},"PeriodicalIF":0.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2542568421000611/pdfft?md5=899968fc321a220f5e08146923b165b7&pid=1-s2.0-S2542568421000611-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47396876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Expert consensus on liver transplantation perioperative evaluation and rehabilitation for acute-on-chronic liver failure 专家共识肝移植围手术期评估和康复治疗急性慢性肝衰竭
Liver Research Pub Date : 2022-09-01 DOI: 10.1016/j.livres.2022.08.002
Haijin Lv , Haiqing Zheng , Jianrong Liu , Qing Cai , Yuji Ren , Huimin Yi , Yang Yang , Xiquan Hu , Guihua Chen , Transplantation Immunology Committee of Branch of Organ Transplantation Physician of Chinese Medical Doctor Association, Organ Transplant Committee of China Association Rehabilitation Medicine, Guangdong Medical Doctor Association of Organ Transplantation
{"title":"Expert consensus on liver transplantation perioperative evaluation and rehabilitation for acute-on-chronic liver failure","authors":"Haijin Lv ,&nbsp;Haiqing Zheng ,&nbsp;Jianrong Liu ,&nbsp;Qing Cai ,&nbsp;Yuji Ren ,&nbsp;Huimin Yi ,&nbsp;Yang Yang ,&nbsp;Xiquan Hu ,&nbsp;Guihua Chen ,&nbsp;Transplantation Immunology Committee of Branch of Organ Transplantation Physician of Chinese Medical Doctor Association,&nbsp;Organ Transplant Committee of China Association Rehabilitation Medicine,&nbsp;Guangdong Medical Doctor Association of Organ Transplantation","doi":"10.1016/j.livres.2022.08.002","DOIUrl":"10.1016/j.livres.2022.08.002","url":null,"abstract":"<div><p>Acute-on-chronic liver failure (ACLF) can be cured by liver transplantation; however, perioperative complications still affect posttransplant outcomes. In recent years, early rehabilitation for critical illness, liver disease, and surgery have significantly improved organ reserve function, surgery tolerance, and postoperative quality of life. They could also be applied in the perioperative period of liver transplantation in patients with ACLF. Therefore, the Transplantation Immunology Committee of Branch of Organ Transplantation Physician of Chinese Medical Doctor Association, the Organ Transplant Committee of China Association Rehabilitation Medicine, and the Guangdong Medical Doctor Association of Organ Transplantation conducted a comprehensive review of rehabilitation in end-stage liver disease, critical illness and surgical patients by summarizing current evidence and best clinical practices and proposed a practice consensus on evaluation of cardiopulmonary and physical function, rehabilitation or physiotherapies, as well as the safety concerns in perioperative liver transplant recipients. It will be a valuable resource for hepatologists, transplant surgeons, and intensivists as they care for ACLF patients during transplantation.</p></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"6 3","pages":"Pages 121-129"},"PeriodicalIF":0.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2542568422000381/pdfft?md5=2cfbc7609777731027494c7738f76764&pid=1-s2.0-S2542568422000381-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41780810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The role of roof plate-specific spondins in liver homeostasis and disease 顶板特异性反应蛋白在肝脏稳态和疾病中的作用
Liver Research Pub Date : 2022-09-01 DOI: 10.1016/j.livres.2022.09.002
Le Yang, Wenhui Yue, Hang Zhang, Yue Gao, Lin Yang, Liying Li
{"title":"The role of roof plate-specific spondins in liver homeostasis and disease","authors":"Le Yang,&nbsp;Wenhui Yue,&nbsp;Hang Zhang,&nbsp;Yue Gao,&nbsp;Lin Yang,&nbsp;Liying Li","doi":"10.1016/j.livres.2022.09.002","DOIUrl":"10.1016/j.livres.2022.09.002","url":null,"abstract":"<div><p>As evolutionarily conserved signals, roof plate-specific spondins (R-spondins; RSPOs) are a family with four members (RSPO1–4) exerting distinctly different functions. RSPOs have five receptors and correlate with different signaling pathways through these receptors and then perform various functions. Moreover, their best-known molecular function is the capacity to enhance WNT signaling pathways, which play critical roles in several processes. A recent study shows that RSPOs not only potentiate the WNT/beta (β)-catenin signaling pathway but are also involved in the WNT/planar cell polarity signaling pathway. RSPOs influence liver homeostasis and the development of multiple liver diseases. RSPO1 increases cell proliferation, protects hepatocytes from injury, improves liver regenerative potential, and affects liver metabolic zonation. RSPO2 not only regulates proliferation-associated genes and promotes differentiation in the liver but also participates in liver fibrosis through the WNT/β-catenin signaling pathway. RSPO3 is a key determinant of proper liver function, such as promoting hepatocyte regeneration and maintaining liver zonation. RSPO3 is upregulated in liver fibrosis and livers of patients with non-alcoholic steatohepatitis. Besides, RSPO2 and RSPO3 are confirmed as oncogenes and involved in the occurrence of liver cancer. The role of RSPO4 in the liver remains unclear. In this review, the structural and biochemical properties of RSPOs and their receptors and their roles in liver homeostasis and disease are summarized.</p></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"6 3","pages":"Pages 139-145"},"PeriodicalIF":0.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2542568422000447/pdfft?md5=f7b452581758742b0a9960c19daf4db6&pid=1-s2.0-S2542568422000447-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48102479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Exosomes as mediators of tumor immune escape and immunotherapy in hepatocellular carcinoma 外泌体作为肝癌肿瘤免疫逃逸和免疫治疗的介质
Liver Research Pub Date : 2022-09-01 DOI: 10.1016/j.livres.2022.08.001
Ming-Cheng Guan , Ming-Da Wang , Wan-Yin Wang , Chao Li , Lan-Qing Yao , Hong Zhu , Tian Yang
{"title":"Exosomes as mediators of tumor immune escape and immunotherapy in hepatocellular carcinoma","authors":"Ming-Cheng Guan ,&nbsp;Ming-Da Wang ,&nbsp;Wan-Yin Wang ,&nbsp;Chao Li ,&nbsp;Lan-Qing Yao ,&nbsp;Hong Zhu ,&nbsp;Tian Yang","doi":"10.1016/j.livres.2022.08.001","DOIUrl":"10.1016/j.livres.2022.08.001","url":null,"abstract":"<div><p>Hepatocellular carcinoma (HCC), a typical inflammatory-related cancer, mainly occurs in patients with chronic liver diseases. Moreover, the liver is an immunologically privileged apparatus with multiple immunosuppressive cell groups. The long process of inflammation-mediated carcinogenesis turns the HCC tumor microenvironment (TME) into one with strong immunosuppression, facilitating the immune escape of HCC cells. Accumulated data have manifested that tumor-associated cell-derived exosomes carry diverse molecular cargoes (<em>e.g.</em>, proteins and nucleic acids) for mediating cell-to-cell communication and are implicated in TME remodeling to promote tumor-infiltrating immune cell reprogramming, ultimately creating a tumor-friendly microenvironment. Characterized by several intrinsic attributes, such as good stability (bilayer-like structure) and high biocompatibility (cell secretion), exosomes can be modified or engineered as nanocarriers to deliver tumor-specific antigens or antitumor drugs to targeted cells or organs, thus effectively triggering the HCC cell elimination by the immune system. This review aimed to highlight the pivotal role of exosomes in regulating immune escape mechanisms in HCC and recent advances in exosome-mediated immunotherapy for HCC.</p></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"6 3","pages":"Pages 132-138"},"PeriodicalIF":0.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S254256842200037X/pdfft?md5=56a87450ba558ab2216462f86afcb8cd&pid=1-s2.0-S254256842200037X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41746433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
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